Diabetes is a group of diseases characterized by chronic hyperglycemia induced by a lack of insulin action, along with various characteristic metabolic abnormalities. Prolonged metabolic abnormalities tend to cause inherent complications and also promote arteriosclerosis. Diabetes can be broadly divided into type I and type II. Type I is characterized by β-cell disruption in pancreatic Langerhans' islets as its onset mechanism, while reductions in both insulin secretion and insulin sensitivity (insulin resistance) are involved in the onset of type II. Pancreatic Langerhans β-cells are one of four secretory cells (α-cells, β-cells, δ-cells and PP cells) constituting Langerhans' islets (pancreatic islets) and secrete insulin.
It is reported that there are about two million diabetic patients in Japan. For treatment of diabetes, diet therapy, exercise therapy and drug therapy including insulin therapy have been used. These therapies enable diabetes to be controlled to some extent, but each therapy still has problems.
Namely, diet therapy prescribes calorie restriction as well as protein restriction for patients whose condition is further complicated by nephropathy, although this therapy should be followed every day over a long period of time. Moreover, as diet therapy is mostly controlled by the patients themselves or their family members, there is a problem that many patients give up continuing the therapy.
Exercise therapy is also important in that it must become an everyday activity of the patient. However, when attention is directed exclusively to exercise therapy while ignoring diet therapy, exercise therapy will have the opposite effect on diabetes control to what was intended, as a result of increased appetite.
In drug therapy, insulin is used for treatment of a part of type I and type II diabetes. However, although insulin therapy has a dramatic effect on the reduction of blood glucose, the therapy requires daily administration of self-injections and is merely a symptomatic treatment. On the other hand, oral hypoglycemic agents include sulfonylurea (SU) drugs and biguanide drugs. However, these drugs have problems such as β-cell exhaustion induced by the random use of SU drugs and side effects of lactic acidosis caused by biguanide drugs. Under present circumstances, all of these drugs are used for symptomatic treatment and there is no therapeutic agent for a radical treatment. Thiazolidine derivatives recently developed as agents for ameliorating insulin resistance also cause many side effects and tend to produce results clearly polarized between effective and non-effective.
At present, based on the concept of radical treatment, attempts have been made to develop β-cell transplantation using embryonic stem cells or differentiation-inducing therapy involving expression of a specific gene in β-cell progenitors within pancreatic tissues, and these attempts have reached the preclinical stage.
Recent studies have indicated that stem cells present in the bone marrow are pluripotent and differentiated into blood vessels or cardiac muscle cells, etc. Likewise, it has been found that bone marrow-derived cells are also differentiated into endodermal tissues such as intestinal cells or pancreatic β-cells and are involved in the regeneration of these tissues.
Human G-CSF is a hematopoietic factor found as a differentiation-inducing factor for hematopoietic stem cells of the granulocytic lineage and is clinically used as a therapeutic agent for neutropenia following bone marrow transplantation or cancer chemotherapy because it promotes in vivo hematopoiesis of neutrophils. In addition to this action, human G-CSF acts on stem cells to stimulate their differentiation and proliferation, and also recruits stem cells from the bone marrow into the peripheral blood. Based on the latter action, in fact, transplantation of the peripheral blood hematopoietic stem cells recruited by human G-CSF, i.e., peripheral blood stem cell transplantation is performed in a clinical setting, with the aim of accelerating hematopoietic recovery in cancer patients after intensive chemotherapy.